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Development 129, 167-174 (2002)
© 2002 The Company of Biologists Limited

Disruption of Gja8 ({alpha}8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation

Pei Rong1, Xin Wang1, Ingrid Niesman1, Ying Wu1, Lucio E. Benedetti2, Irene Dunia2, Esther Levy1 and Xiaohua Gong1,*

1 Department of Cell Biology, The Scripps Research Institute, La Jolla, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
2 Institut Jacques Monod, University Paris VII, Paris, France

*Author for correspondence (e-mail: gong{at}scripps.edu)

Accepted 3 October 2001

The development of the vertebrate lens utilizes a sophisticated cell-cell communication network via gap junction channels, which are made up of at least three connexin isoforms, {alpha}8 (Cx50), {alpha}3 (Cx46) and {alpha}1 (Cx43), and which are encoded by three different genes. In a previous study, we reported that, with a disruption of Gja3 ({alpha}3 connexin), mice developed nuclear cataracts with a normal sized lens. We show that Gja8tm1 ({alpha}8–/–) mice develop microphthalmia with small lenses and nuclear cataracts, while the {alpha}8 heterozygous (+/–) mice have relatively normal eyes and lenses. A comparative study of these {alpha}3 and {alpha}8 knockout mice showed that the protein levels of both {alpha}3 and {alpha}8 were independently regulated and there was no compensation for either the {alpha}3 or {alpha}8 protein from the wild-type allele when the other allele was disrupted. More interestingly, western blotting data indicated that the presence of {alpha}8 in the lens nucleus is dependent on {alpha}3 connexin, but not vice versa. The staining of the knock-in lacZ reporter gene showed the promoter activity of {alpha}8 connexin is much higher than that of {alpha}3 connexin in embryonic lenses and in adult lens epithelium. More importantly, a delayed denucleation process was observed in the interior fibers of the {alpha}8–/– lenses. Therefore, {alpha}8 connexin is required for proper fiber cell maturation and control of lens size.

Key words: Connexin, Lens, Microphthalmia, Cataract, Mouse




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© The Company of Biologists Ltd 2002